GSE129696 Downregulation of polycomb repressive complex 2 mediates cisplatin acquired resistant in testicular germ cell tumors

Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensA greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. More than 80% of metastatic TGCT patients are cured with cisplatin-based chemotherapy. However, resistance can occur, which results in poor outcomes. The mechanisms of cisplatin hypersensitivity and resistance in these tumors and embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisplatin acquired resistance we generated a large panel of independently derived, acquired resistant clones from three distinct parental EC models employing a protocol designed to match standard of care regimens of TGCT patients. Transcriptomics revealed highly significant alterations shared between resistant cells regardless of their parental origin. This included a highly significant enrichment of genes normally repressed by H3K27 methylation and the polycomb repressive complex 2 (PRC2) which correlated with a substantial decrease in global H3K27me3, H2AK119 ubiquitination and expression of BMI1. Importantly repression of H3K27 methylation with the EZH2 inhibitor GSK-126 conferred cisplatin resistance to parental cells while induction of H3K27 methylation with the histone lysine demethylase inhibitor GSK-J4 resulted in increased cisplatin sensitivity to resis...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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In conclusion, NKX3.1 shows routine expression in Sertoli cells and P501S shows routine expression in Leydig cells and rete testis epithelium. In addition, these markers can be positive in sex cord-stromal tumors and rete testis adenocarcinoma.
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research
CONCLUSIONS: The differences in the expression of nucleolin between two groups of germ cell testicular tumors found in the current study indicate a new aspect of biology of these neoplasms and require further studies on the role of nucleolin in germ cell tumorigenesis. PMID: 31513277 [PubMed - as supplied by publisher]
Source: Folia Histochemica et Cytobiologica - Category: Cytology Tags: Folia Histochem Cytobiol Source Type: research
chael J. Spinella A greater understanding of the hypersensitivity and curability of testicular germ cell tumors (TGCTs) has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. The mechanisms of cisplatin hypersensitivity and resistance in embryonal carcinoma (EC), the stem cells of TGCTs, remain largely undefined. To study the mechanisms of cisplatin resistance we generated a large panel of independently derived, acquired resistant clones from three distinct parental EC models employing a protocol designed to match standard of care regimens of TGCT patients. Transcriptomic...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we generated TCam-2 cells double-deficient for SOX2 and FOXA2 using the CRISPR/Cas9 technique and xenografted those cells into the flank of nude mice. Upon loss of SOX2 and FOXA2, TCam-2 maintained a seminoma cell fate for at least twelve weeks, demonstrating that both factors are key players in the reprogramming to an EC-like cell fate. Therefore, our study adds an important piece to the puzzle of GCT development and plasticity, providing interesting insights in what can be expected in a patient, when GCT cells are confronted with different microenvironments.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionOur findings highlight the value of cross ‐species comparative oncology for the identification of candidate human cancer genes.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: Original Article Source Type: research
Katarina Rejlekova1, Maria C. Cursano2, Ugo De Giorgi3 and Michal Mego1* 12nd Department of Oncology, Faculty of Medicine, National Cancer Institute, Comenius University, Bratislava, Slovakia 2Oncology Unit, Università Campus Bio-Medico, Rome, Italy 3Medical Oncology Department, Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola, Italy Testicular germ cell tumors (TGCTs) represent the most common solid tumor in young men and is a model of curable cancer. The effectiveness of cisplatin-based chemotherapy secures more than 95% of patients' 5-years survival rate. Howeve...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Abstract In 2016, the WHO classification of testicular germ cell tumors was revised considering advances in the understanding of their tumorigenesis and molecular features. This restructuring led to a division into two major groups with, on one hand, prepubertal-type tumors, not derived from germ cell neoplasia in situ (GCNIS), and on the other hand, postpubertal-type tumors, GCNIS-derived, which occur in youg men (seminoma and non seminomatous germ cell tumors - embryonal carcinoma, yolk sac tumor, teratoma and choriocarcinoma essentially). The term germ cell neoplasia in situ is consensually accepted as a new te...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
CONCLUSION: Finally, the pathogenesis of testicular germ cell tumor needs to be deeply understood so that it will improve data on stem cells, tumorigenesis and disease tumor management by more selective treatment. PMID: 30636617 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Cancer Drug Discovery - Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
Discussion and conclusionsPopulation ‐based incidence time trends for seminomatous and non‐seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non‐seminomatous TGCTs ar e examined.
Source: Andrology - Category: Urology & Nephrology Authors: Tags: Original Article Source Type: research
MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGC...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
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